Alkylation of aromatic aldehydes with alkylboron chloride derivatives

Article abstract of DOI:10.1016/S0040-4020(00)01160-1

The reaction of aryl aldehydes with alkylboron chlorides has been investigated. Monoalkylboron dichlorides react with aryl aldehydes in hexane under reflux conditions to give a mixture of dichloroarylmethane and benzyl chloride. Under the same reaction conditions, dialkylboron chlorides lead to formation of a mixture of benzyl chloride and the chloroalkylation product. In the presence of a base such as 2,6-lutidine, the reactions of monoalkylboron dichlorides with aryl aldehydes yield small amounts of the desired alkylation products at room temperature. Dialkylboron chlorides react with aryl aldehydes in hexane in the presence of base to generate the corresponding arylalkylmethanols in good yields.

Full text of DOI:10.1016/S0040-4020(00)01160-1

TETRAHEDRON
Pergamon
Tetrahedron 57 (2001) 1663±1670
Alkylation of aromatic aldehydes with
alkylboron chloride derivatives
George W. Kabalka,p Zhongzhi Wu and Yuhong Ju
Departments of Chemistry and Radiology, The University of Tennessee, Knoxville, TN 37996-1600, USA
Received 13 September 2000; accepted 15 December 2000
AbstractÐThe reaction of aryl aldehydes with alkylboron chlorides has been investigated. Monoalkylboron dichlorides react with aryl
aldehydes in hexane under re¯ux conditions to give a mixture of dichloroarylmethane and benzyl chloride. Under the same reaction
conditions, dialkylboron chlorides lead to formation of a mixture of benzyl chloride and the chloroalkylation product. In the presence of
a base such as 2,6-lutidine, the reactions of monoalkylboron dichlorides with aryl aldehydes yield small amounts of the desired alkylation
products at room temperature. Dialkylboron chlorides react with aryl aldehydes in hexane in the presence of base to generate the
corresponding arylalkylmethanols in good yields. q 2001 Elsevier Science Ltd. All rights reserved.
1. Introduction
reagents have not been used to alkylate carbonyl
compounds. We recently reported the initial results of a
study involving the alkylation of aryl aldehydes using alkyl-
boron chloride derivatives to produce the corresponding
alcohols in good yields (Scheme 1).35 We now wish to
report the results of a detailed study of this new reaction.
Generally, only reactive alkylmetals such as the organo-
magnesium,1±4 organolithium,5 organozinc6,7 and certain
organotransition metal reagents8±15 can be utilized to alkyl-
ate carbonyl compounds, one of the most important carbon±
carbon bond forming reactions. Organoboranes do not
normally react with carbonyl compounds in a Grignard-
like fashion with the exception of allylborane and vinyl-
borane reagents.16±19 The few known alkylborane carbonyl
alkylation reactions require reactive organoboranes,20 free
radical conditions,21,22 or activation of the carbonyl
groups.23,24 However, a Grignard-like reaction involving
organoborane reagents would possess a number of synthetic
advantages including mild reaction conditions, stereo-
chemical control and the fact that a large number of func-
tional substituents are unaffected in most organoborane
transformations.25±30
2. Results and discussion
2.1. The reaction of alkylboron dichlorides with aryl
aldehydes
Earlier, we reported a new method for converting aryl
aldehydes into dichloroarylmethanes using boron tri-
chloride.36,37 The reaction appears to proceed via an alkoxy-
boron chloride intermediate (Scheme 2). It occurred to us
that the use of an alkylboron derivative in place of boron
trichloride could lead to a new alkylation reaction, which
would provide a Grignard-like addition reaction. We thus
examined the reaction of alkylboron dichloride reagents
with aryl aldehydes but found that no reaction occurred in
hexane solution at room temperature. However, a mixture of
benzyl chloride and dichoromethylbenzene was formed
when the reaction mixture was re¯uxed in hexane. This
result indicates that, in addition to the formation of dichloro-
arylmethane, a reductive chlorination reaction occurs
(Scheme 3). The formation of dichloroarylmethane presum-
ably occurs via the pathway reported for reactions of BCl3
with aryl aldehydes.36 However, the generation of benzyl
chloride could occur via two reaction pathways, as has been
observed in the reaction of dialkylboron bromide with aryl
aldehydes38 (Scheme 3). The use of phenylboron dichloride
(which has no transferable beta-hydrogens) results in the
exclusive formation of dichloromethylbenzene.
Boron halide derivatives have been used extensively in bond
cleavage reactions31 and as enolate reagents for use in the
aldol reactions. Boron enolates are particularly useful in
diastereoselective and enantioselective carbon±carbon
bond formation.32±34 However, organic boron halide
Scheme 1. Alkylation of aryl aldehydes.
Keywords: boron and compounds; aldehydes; alcohols; alkylation.
Corresponding author. Tel.: 11-865-974-3260; fax: 11-865-974-2997;
e-mail: kabalka@utk.edu
p
0040±4020/01/$ - see front matter q 2001 Elsevier Science Ltd. All rights reserved.
PII: S0040-4020(00)01160-1

1664
G. W. Kabalka et al. / Tetrahedron 57 (2001) 1663±1670
Scheme 2. Chlorination of aryl aldehydes via BCl3.
Scheme 3. Reaction of aryl aldehydes with RBCl2 under re¯ux conditions.
The reaction of n-butylboron dichloride with benzaldehyde
leads to the formation of a small amount of the desired
alkylation product if the reaction is carried out in the
presence of a base such as triethylamine, quinuclidine or
2,6-lutidine. In the case of 2,6-lutidine, a 15% yield of
1-phenylpentanol can be isolated from the reaction mixture.
Attempts to increase the yield of the alkylation product have
been unsuccessful.
The reaction was then carried out in hexane at re¯ux.
Surprisingly, the chloroalkylation product, chlorocyclo-
hexylphenylmethane, was formed along with benzyl
chloride. However, the yield of the chloroalkylation product
was modest (25% isolated yield). The formation of benzyl
chloride was not unexpected and had been observed in the
reaction of n-butylboron dichloride with aryl aldehydes. The
formation of chloroalkylation product is unprecedented.
Possible reaction pathways are presented in Scheme 4.
Attempts to increase the yield of chloroalkylation products
were unsuccessful.
2.2. The reaction of dialkylboron chlorides with aryl
aldehydes under re¯ux conditions
Since the reactions of alkylboron dichloride reagents with
aryl aldehydes did not lead to signi®cant yields of alkylation
products, we studied the reactions of dialkylboron chloride
derivatives with aldehydes. We ®rst examined the reaction
of dicyclohexylboron chloride with benzaldehyde in hexane
at room temperature and found that no reaction occurred.
2.3. The reaction of dialkylboron chlorides with aryl
aldehydes in the presence of base
The reaction of dialkylboron chlorides with aryl aldehydes
was then examined in the presence of various bases.
Moderate to good yields of desired alkylation products,

G. W. Kabalka et al. / Tetrahedron 57 (2001) 1663±1670
1665
Scheme 4. Reaction of aryl aldehydes with R2BCl under re¯ux conditions.
arylalkylmethanols, were obtained. In order to investigate
the reaction mechanism, the reaction of 4-bromobenzalde-
hyde with dicyclohexylboron chloride was monitored by
NMR spectroscopy. Dicyclohexylboron chloride (1 M
hexane solution) was added to 4-bromobenzaldehyde in
hexane at 2308C. The solvent was removed under reduced
pressure to yield a yellow solid, which was then dissolved in
benzene-d6 for NMR analysis at room temperature. The
characteristic 1H and 13C resonances for the aldehyde
were absent in the resultant NMR spectra. Interestingly,
no new resonances appeared in the 1H and 13C NMR spectra.
Furthermore, upon addition of water (instead of a base),
4-bromobenzaldehyde was regenerated. These results
suggest that 4-bromobenzaldehyde coordinates to dicyclo-
hexylboron chloride. In a separate experiment, upon addition
of Et3N to the benzene-d6 solution of the reaction mixture, a
new doublet appeared at 5.11 ppm in the 1H NMR and a new
13C NMR resonance appeared at 83.4 ppm. Hydrolysis of
this reaction mixture lead to the formation of the alkylation
product cyclohexyl(4-bromophenyl)methanol. In a third
NMR experiment, the benzene solution of the aldehyde
and boron chloride was examined by 11B NMR which
revealed a resonance at 64.4 ppm (slightly up®eld of the
resonance at 78 ppm for dicyclohexylboron chloride) indi-
cating a weak coordination of aldehyde with boron. Upon
addition of Et3N, the 11B NMR signal shifted to 12.8 ppm,
suggesting coordination of the amine to boron. However,
the 11B NMR data do not provide information about the
reaction intermediate. On the basis of the NMR data, the
alkylation of aldehydes presumably proceeds via coordina-
tion of the carbonyl to boron followed by migration of the
alkyl group (Scheme 5).
was noted that benzyl alcohols were also formed in small
quantities along with the desired alkylated product in all the
chloroborane reactions. Moreover, reduction of the
aldehydes predominated if the more hindered boron
reagents such as di(3-methyl-2-butyl)boron chloride,
di(exo-norbornyl)boron chloride and DIP-chloride were
utilized; these organoboranes have been widely used as an
effective reducing reagent for carbonyl compounds.39
A series of aromatic aldehydes was subjected to the new
alkylation reaction. Essentially all aldehydes examined
were converted successfully to the corresponding aryl-
alkylmethanols, Table 1. In the case of anisaldehyde,
cleavage of the ether group did not occur.31 Also, the
cyano group was unaffected.40 From the data in Table 1, it
can be seen that boranes containing primary alkyl groups
produce relatively low yields of the desired product
compared to those containing secondary alkyl groups.
Although it is not clear what leads to low yields for boranes
containing primary alkyl groups, it could be a consequence
of steric effects. We did ®nd that the alkylation of aldehydes
The reaction of tri(n-butyl)borane with aryl aldehydes was
then investigated at re¯ux in the presence of base. It was
discovered that no alkylation reaction occurred under these
conditions. The results suggest that the chloride atom plays
a critical role in the alkylation reactions. Compared to tri-
alkylboranes, chloroboranes are more electron-de®cient and
can coordinate more effectively to the carbonyl oxygen. It
Scheme 5. Alkylation of aryl aldehydes via R2BCl in presence of base.

1666
G. W. Kabalka et al. / Tetrahedron 57 (2001) 1663±1670
Table 1. Synthesis of 1-phenyl-1-alkanols via reaction of aromatic
aldehydes with R2BCl
Table 2. Reaction of 4-bromobenzaldehyde with dicyclohexylboron chlo-
ride in the presence of various bases
Entry
X
R
Product
% Yield 3a
Entry
Base
Product
Yield (%)
1
2
3
4
5
6
7
8
1a (H)
1b (4-F)
Cyclohexyl
Cyclohexyl
Cyclohexyl
Cyclohexyl
Cyclohexyl
Cyclohexyl
Cyclohexyl
Cyclohexyl
Cyclohexyl
Cyclohexyl
Cyclohexyl
Cyclopentyl
Cyclopentyl
Cyclopentyl
Cyclopentyl
Norbornyl
Norbornyl
Norbornyl
s-Butyl
s-Butyl
s-Butyl
s-Butyl
s-Butyl
s-Butyl
1-Hexyl
1-Hexyl
1-Hexyl
3a
3b
3c
3d
3e
75
90
78
49
76
65
78
83
86
27
66
65
78
70
60
25
28
25
60
75
70
79
67
20
35
70
41
30
40
30
25
1
2
3
4
5
6
7
Et3N
3e
3e
3e
3e
3e
3e
3e
60
74
40
76
76
72
76
Quinuclidine
Pyridine
2,6-Lutidine
DBU
1c (4-Cl)
1d (2-Cl)
1e (4-Br)
1f (2-Me)
1g (4-Me)
1h (4-MeO)
1i (4-NC)
1j (Naphthyl)
1k (4-CHO)
1l (H)
1m (4-F)
1n (4-Cl)
1o (4-Me)
1p (H)
1q (4-Br)
1r (4-Me)
1s (H)
3f
BunLi
3g
3h
3i
3j
3k
3l
3m
3n
3o
3p
3q
3r
ButOK
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
3. Conclusions
The new alkylation reaction provides a potentially useful
alternative to traditional Grignard and organolithium
reactions. The reaction occurs under mild reaction condi-
tions and tolerates a variety of functional groups. It is
limited to aldehydes that do not possess a-hydrogens due
to the well-known enolization reactions that occur with
dialkylboron halides. Benzyl alcohols are formed in small
quantities along with the desired products; this reaction
predominates if the more hindered organoboranes, such as
3s
3t
1t (4-F)
1u (4-Cl)
1v (4-Br)
1w (4-Me)
1x (2-Me)
1y (H)
3u
3v
3w
3x
3y
3z
3aa
3ab
3ac
3ad
3ae
diisopinocampheylboron
chloride,
dinorbornylboron
chloride, and di-(3-methyl-2-butyl)boron chloride are
utilized. Organoboron chlorides containing secondary
alkyl groups tend to give higher yield of alkylation products.
Bulkier bases also lead to higher yield of alkylated products.
1z (4-F)
1aa (4-Cl)
1ab (2-Cl)
1ac (4-Br)
1ad (4-Me)
1ae (2-Me)
1-Hexyl
1-Hexyl
1-Hexyl
1-Hexyl
a
Isolated yields based on starting aldehydes.
4. Experimental
via boranes containing primary alkyl groups was
much slower than reactions involving boranes containing
secondary alkyl groups. In one reaction, 4-bromobenzalde-
hyde was allowed to react with cyclohexyl(n-butyl)boron
chloride. As anticipated, the major product was cyclo-
hexyl(4-bromophenyl)methanol (58% isolated yield)
(Scheme 6).
All glassware and equipment were dried in an oven heated
to 2508C for at least 12 h and cooled under argon prior to
use. All solvents were distilled from appropriate drying
agents prior to use. Reactions were stirred magnetically
and monitored by TLC. Products were puri®ed by ¯ash
chromatography using silica gel (230±400 mesh, 60 A,
ICN Biomedical GmbH, Eschwege, Germany), with
dichloromethane as eluent.
Ê
Although the role of base in the reaction is not clear, it could
coordinate boron to increase steric crowding and thus
induce the migration of an alkyl group. Alternatively, coor-
dination of the base to the electron-de®cient boron atom
could increase the electron density on boron and facilitate
the migration of the alkyl group. Table 2 contains a
summary of the reaction of 4-bromobenzaldehyde with
dicyclohexylboron chloride in the presence of a variety of
bases. It can be seen that all bases result in the formation of
the desired product. Bulky bases tend to produce higher
yield of products, which is consistent with results noted
earlier. Strong nucleophiles, such as n-butyllithium also
lead to higher yields of products.
Dicyclohexylboron chloride (1.0 M hexane solution) and
n-butyl dichloride (1.0 M hexane solution) were purchased
from Aldrich Chemical Co. Dihexylboron chloride, di(exo-
norbornyl)boron chloride, dicyclopentylboron chloride, and
di-sec-butylboron
chloride
were
prepared
from
H2BCl´SMe2 and the corresponding alkenes (1-hexene,
norbornylene, cyclopentene, cis-2-butene) according to the
literature procedures.40 Cyclohexyl(n-butyl)boron chloride
was prepared via reaction of n-butylboron dichloride with
cyclohexene and triethylsilane.41 All aldehydes (Aldrich
Chemical Co.) were dried and distilled under argon.
Triethylamine, 2,6-lutidine, quinuclidine, and DBU were
Scheme 6. Alkylation of p-bromobenzaldehyde using cyclohexyl(n-butyl)boron chloride

G. W. Kabalka et al. / Tetrahedron 57 (2001) 1663±1670
1667
dried and distilled prior to use. n-Butyllithium and lithium
t-butoxide (Aldrich Chemical Co.) were used as received.
3.0 mL of a 1.0 M hexane solution) was added via syringe
and the solution allowed to stir for 30 min at room tempera-
ture. 2,6-Lutidine (3.0 mmol, 0.32 g) was then added and
the mixture stirred for 5 h. A precipitate was formed, which
contained boron. Hydrolysis, as well as oxidation, of the
remaining alkylboron group was accomplished by addition
of hydrogen peroxide (0.5 mL of a 30% aqueous solution)
and sodium hydroxide (3.0 mmol, 1.0 mL of a 3.0 M
aqueous solution). [Alternatively, water could be added
and the product isolated from the organic phase.] After
separation of the organic layer, 0.43 g of the desired product
(75% yield) was isolated by column chromatography.
All melting points are uncorrected. Elemental analyses were
performed by Atlantic Microlabs, Norcross, GA. NMR
spectra were measured in CDCl3 or C6D6 at 250 MHz (1H)
or at 62.9 MHz (13C). In cases where more than one isomer
formed, the NMR shifts of all isomers are reported. Chemi-
cal shifts are referenced to TMS. HR-EI-MS were obtained
using a ZAB-EQ instrument.
4.1. Reaction of aryl aldehydes with alkylboron
dichlorides in hexane
4.4.1. Cyclohexylphenylmethanol (3a). Colorless oil.44 1
H
NMR: d 7.36±7.23 (m, 5H), 4.35 (d, 1H, Jˆ7.2 Hz), 1.90 (s,
1H), 2.01±0.94 (m, 11H). 13C NMR: d 143.6, 128.2, 127.4,
126.6, 79.4, 44.9, 29.3, 28.8, 26.4, 26.1, 26.0.
The reaction of n-butylboron dichloride with benzaldehyde
is representative. Benzaldehyde (5.0 mmol, 0.53 g) was
dissolved in hexane (10 mL) contained in a dry, argon-
¯ushed, 50 mL round-bottomed ¯ask. n-Butylboron
dichloride (5.0 mmol, 5.0 mL of a 1.0 M hexane solution)
was added via syringe and the solution was allowed to react
at re¯ux for 3 h. Hydrolysis, separation of the organic layer
and column chromatography afforded a mixture of dichloro-
toluene and benzyl chloride (2:3 ratio).
4.4.2. Cyclohexyl(4-¯uorophenyl)methanol (3b). Color-
less oil. H NMR: d 7.21±6.93 (m, 4H), 4.25 (d, 0.5H,
1
Jˆ4.4 Hz), 4.23 (d, 0.5H, Jˆ4.4 Hz), 2.65 (s, 1H), 1.93±
0.81 (m, 11H). 13C NMR: d 163.9, 160.0, 139.3, 139.2,
128.1, 128.0, 114.56, 114.6, 78.5, 44.9, 29.0, 28.8, 26.3,
25.9. Anal. Calcd for C13H17OF: C, 74.97; H, 8.23. Found:
C, 74.85; H, 8.24.
4.2. Reaction of aryl aldehydes with dialkylboron
chlorides
4.4.3. Cyclohexyl(4-chlorophenyl)methanol (3c). White
1
solid; mp 73±748C (lit.45; 74±758C). H NMR: d 7.27 (d,
The reaction of dicyclohexylboron chloride with benzalde-
hyde is representative. Benzaldehyde (5.0 mmol, 0.53 g)
was dissolved in hexane (10 mL) contained in a dry,
argon-¯ushed, 50 mL round-bottomed ¯ask. Dicyclohexyl-
boron chloride (5.0 mmol, 5.0 mL of a 1.0 M hexane solu-
tion) was added via syringe, and the solution allowed to
re¯ux for 4 h. Hydrolysis, separation of the organic layer
and column chromatography afforded 0.12 g of benzyl
chloride (15%) and 0.26 g of chlorocyclohexylphenyl-
methane (25%).42 NMR data for chlorocyclohexylphenyl-
methane; 1H NMR: d 7.33±7.22 (m, 5H), 4.60 (d,
Jˆ8.41 Hz, 1H), 2.21±0.86 (m, 11H); 13C NMR: d 140.9,
128.3, 127.9, 127.5, 69.8, 45.7, 30.4, 30.3, 26.11, 25.9, 25.9.
2H, Jˆ7.5 Hz), 7.17 (d, 2H, Jˆ8.2 Hz), 4.28 (d, 1H,
Jˆ6.8 Hz), 2.31(s, 1H), 1.91±0.85 (m, 11H). 13C NMR: d
142.0, 132.9, 128.2, 127.9, 78.5, 44.9, 29.1, 28.6, 26.3, 25.9.
4.4.4. Cyclohexyl(2-chlorophenyl)methanol (3d). White
solid; mp 85±868C. H NMR: d 7.48±7.13 (m, 4H), 4.90
1
(d, 0.5H, Jˆ3.7 Hz), 4.87 (d, 0.5H, Jˆ3.7 Hz), 2.10 (d, 1H,
Jˆ3.7 Hz), 1.87±1.08 (m, 11H). 13C NMR d 141.1, 132.4,
129.3, 128.2, 128.1, 126.7, 74.9, 43.9, 29.4, 27.8, 26.3, 26.2,
26.0. Anal. Calcd for C13H17OCl: C, 69.48; H, 7.62. Found:
C, 69.27; H, 7.67.
4.4.5. Cyclohexyl(4-bromophenyl)methanol (3e). White
1
solid; mp 70±718C (lit.45 71.5±72.58C). H NMR: d 7.26
4.3. Reaction of aryl aldehydes with alkylboron
dichlorides in the presence of base
(d, 2H, Jˆ6.9 Hz), 7.16 (d, 2H, Jˆ7.0 Hz), 4.34 (d, 1H,
Jˆ6.9 Hz), 1.90 (s, 1H), 1.73±0.93 (m, 11H). 13C NMR:
d 142.6, 131.2, 128.3, 121.1, 78.6, 45.0, 29.2, 28.6, 26.4,
26.2, 26.0.
The reaction of n-butylboron dichloride with benzaldehyde
is representative. Benzaldehyde (3.0 mmol, 0.32 g) was
dissolved in hexane (10 mL) contained in a dry, argon-
¯ushed, 50 mL round-bottomed ¯ask. n-Butylboron
dichloride (3.0 mmol, 3.0 mL of a 1.0 M hexane solution)
was added via syringe and the solution allowed to stir for
10 h at room temperature. 2,6-Lutidine (3.0 mmol, 0.32 g)
was then added and the mixture stirred at room temperature
for 12 h. The reaction mixture was hydrolyzed, the organic
layer separated and then dried over anhydrous MgSO4.
The desired product, 1-phenylpentanol,43 was isolated by
column chromatography in 15% yield.
4.4.6. Cyclohexyl(o-tolyl)methanol (3f). Colorless oil.46
1H NMR: d 7.38±7.08 (m, 4H), 4.60 (d, 1H, Jˆ7.1 Hz),
2.29 (s, 3H), 1.99±1.03 (m, 12H). 13C NMR: d 142.0,
135.0, 130.2, 127.0, 126.2, 126.00, 75.0, 44.5, 29.5, 28.5,
26.3, 26.0, 19.4.
4.4.7. Cyclohexyl( p-tolyl)methanol (3g). White solid; mp
41±428C (lit.47 41±428C). 1H NMR: d 7.16 (d, 2H,
Jˆ8.3 Hz), 7.11 (d, 2H, Jˆ8.3 Hz), 4.27 (d, 1H,
Jˆ7.0 Hz), 2.32 (s, 3H), 1.99 (s, 1H), 1.95±0.90 (m,
11H). 13C NMR: d 140.7, 136.9, 128.8, 126.5, 79.1, 44.8,
29.2, 28.9, 26.4, 26.00, 21.0.
4.4. General procedure for synthesis of alkylaryl
alcohols
4.4.8. Cyclohexyl(4-methoxyphenyl)methanol (3h).
Benzaldehyde (3.0 mmol, 0.32 g) was dissolved in hexane
(10 mL) contained in a dry, argon-¯ushed, 50 mL round-
bottomed ¯ask. Dicyclohexylboron chloride (3.0 mmol,
1
White solid; mp 81±828C (lit.48 82±838C). H NMR: d
7.21 (d, 2H, Jˆ8.4 Hz), 6.86 (d, 2H, Jˆ8.8 Hz), 4.29 (d,

1668
G. W. Kabalka et al. / Tetrahedron 57 (2001) 1663±1670
1H, Jˆ7.6 Hz), 3.80 (s, 1H), 2.02±1.03 (m, 12H). 13C
NMR: d 158.9, 135.8, 127.7, 113.5, 79.0, 55.2, 44.9, 29.2,
29.1, 26.4, 26.1, 26.0.
131.4, 128.9, 128.4, 121.4, 121.3, 78.2, 77.3, 50.2, 49.5,
38.8, 38.3, 36.9, 35.9, 35.4, 34.3, 30.1, 29.9, 28.6. HRMS:
Calcd for C14H17OBr[M]1, 280.046. Found: m/z 280.045.
Anal. Calcd for C14H17OBr: C, 59.80; H, 6.09. Found: C,
59.99; H, 6.15.
4.4.9. Cyclohexyl(4-cyanophenyl)methanol (3i). White
1
solid; mp 82±838C. H NMR: d 7.61 (d, 2H, Jˆ8.3 Hz),
7.41 (d, 2H, Jˆ8.3 Hz), 4.48 (d, 0.5H, Jˆ2.5 Hz), 4.45 (d,
0.5H, Jˆ2.5 Hz), 2.17 (d, 1H, Jˆ3.0 Hz), 1.85±0.94 (m,
11H). 13C NMR: d 148.9, 131.9, 127.3, 118.9, 110.9,
78.3, 45.0, 29.2, 28.1, 26.2, 26.0, 25.9. Anal. Calcd for
C14H17NO: C, 78.10; H, 7.96; N, 6.51. Found: C, 77.86;
H, 7.97; N, 6.54.
4.4.18. 2-Norbornyl-( p-tolyl)methanol (3r). Colorless oil;
1H NMR d 7.244±7.10 (m, 4H), 4.16 (d, 0.4H, Jˆ9.8 Hz),
4.10 (d, 0.6H, Jˆ10.1 Hz), 2.33 (s, 3H), 2.51±0.85 (m,
12H); 13C NMR d 141.6, 140.1, 137.3, 137.1, 128.9,
127.2, 126.6, 78.7, 77.8, 50.0, 49.3, 38.8, 38.4, 37.0, 36.5,
35.4, 34.4, 30.0, 28.7, 21.1. HRMS: Calcd for
C15H20O[M]1, 216.151. Found: m/z 216.150. Anal. Calcd
for C15H20O: C, 83.28; H, 9.32. Found: C, 83.00; H, 9.43.
4.4.10. Cyclohexyl(naphthyl)methanol (3j). Colorless
oil.49 1H NMR: d 8.10±7.37 (m, 7H), 5.10 (d, 1H,
Jˆ6.2 Hz), 2.14 (s, 1H), 1.89±0.85 (m, 11H). 13C NMR:
d 139.5, 133.8, 130.8, 128.8, 127.7, 125.7, 125.3, 125.2,
124.1, 123.6, 75.9, 44.3, 30.2, 28.2, 26.4, 26.3, 26.0.
4.4.19. 2-Methyl-1-phenylbutan-1-ol (3s). Colorless oil.52
1H NMR: d 7.35±7.24 (m, 5H), 4.49 (d, 0.45 H, Jˆ6.0 Hz),
4.40 (d, 0.55 H, Jˆ7.3 Hz), 1.99 (s, 1H), 1.78±0.84 (m, 6H),
0.73(d, 3H, Jˆ6.9 Hz). 13C NMR: d 143.9, 143.6, 128.1,
127.8, 127.3, 127.2, 126.7, 126.4, 78.7, 78.0, 41.9, 41.6,
25.8, 24.8, 15.0, 14.0, 11.6, 11.3.
4.4.11. 1,4-Benzenedi(cyclohexylmethanol) (3k). White
1
solid; mp 153±1548C. H NMR: d 7.25(s, 4H), 4.35 (d,
2H, Jˆ7.2 Hz), 2.00±0.88 (m, 24H). 13C NMR: d 142.8,
126.5, 79.2, 44.9, 29.3, 28.8, 26.4, 26.0. HR-EI-MS:
Calcd for C20H26 [M22H2O]1, 266.2035. Found: m/z
266.2046.
4.4.20.
2-Methyl-1-(4-¯uorophenyl)butan-1-ol
(3t).
1
Colorless oil. H NMR: d 7.22±6.90 (m, 4H), 4.42, (d,
0.40H, Jˆ5.9 Hz), 4.34 (d, 0.60 H, Jˆ6.9 Hz), 2.07 (s,
1H), 1.64±0.67 (m, 6H), 0.65 (d, 3H, Jˆ6.8 Hz). 13C
NMR: d 164.0, 163.9, 160.1, 160.0, 139.5, 139.3, 139.2,
128.3, 128.1, 127.9, 127.8, 115.0, 114.7, 78.0, 77.5, 42.0,
41.7, 25.7, 24.8, 14.9, 13.9, 11.6, 11.2. HR-EI-MS: Calcd
for C11H13F [M2H2O]1, 164.1001. Found: m/z 164.0996.
4.4.12. Cyclopentyl-phenylmethanol (3l). Colorless
liquid;50 1H NMR d 7.34±7.25 (m, 5H), 4.38 (d, 1H,
Jˆ8.4 Hz), 2.56±1.15 (m, 10H); 13C NMR d 144.4, 128.3,
127.5, 126.4, 79.1, 47.6, 29.4, 25.5, 25.4.
4.4.13. Cyclopentyl-(4-¯uorophenyl)methanol (3m).
4.4.21. 2-Methyl-1-(4-chlorophenyl)butan-1-ol (3u).
Colorless oil.53 1H NMR: d 7.29 (d, 2H, Jˆ8.6 Hz), 7.21
(d, 2H, Jˆ8.4 Hz), 4.49 (d, 0.45 H, Jˆ5.09 Hz), 4.39 (d,
0.55 H, Jˆ6.7 Hz), 2.07 (s, 1H), 1.74±0.85 (m, 6H), 0.72 (d,
3H, Jˆ6.8 Hz). 13C NMR: d 142.3, 141.9, 132.9, 132.7,
128.2, 128.0, 127.7, 78.0, 77.2, 41.9, 41.6, 25.7, 24.7,
14.9, 13.8, 11.6, 11.3.
1
Colorless liquid; H NMR d 7.31±7.25 (m 2H), 7.03±6.96
(m, 2H), 4.35 (d, 1H, Jˆ8.4 Hz), 2.20±1.02 (m, 10H); 13C
NMR d 164.0, 160.1, 140.2, 128.1, 127.9, 115.2, 114.8,
78.4, 47.7, 29.4, 25.4, 25.3. HRMS: Calcd for
C12H15OF[M]1, 194.11. Found: m/z 194.111. Anal. Calcd
for C12H15OF: C, 74.20; H, 7.78. Found: C, 74.21, H, 7.89.
4.4.14. Cyclopentyl-(4-chlorophenyl)methanol (3n).
Colorless liquid;50 1H NMR d 7.26 (dd, 4H, Jˆ8.7 Hz),
4.34 (d, 1H, Jˆ8.3 Hz), 2.25 (s, 1H), 2.21±1.06 (m, 9H);
13C NMR d 142.8, 133.0, 128.3, 127.8, 79.2, 47.6, 29.3,
25.4 25.3.
4.4.22. 2-Methyl-1-(4-bromophenyl)butan-1-ol (3v).
1
Colorless oil. H NMR: d 7.42 (d, 2H, Jˆ8.3 Hz), 7.12 (d,
2H, Jˆ8.1 Hz), 4.43 (d, 0.45 H, Jˆ5.2 Hz), 4.34 (d,0.55 H,
6.1 Hz), 2.39 (d, 1H, Jˆ2.5 Hz), 1.68±0.84 (m, 6H), 0.70 (d,
3H, Jˆ6.7 Hz). 13C NMR: d 142.78, 142.7, 131.1, 128.3,
128.0, 121.0, 120.8, 77.9, 77.1, 41.8, 41.5, 25.7, 24.7, 14.8,
13.7, 11.6, 11.22. Anal. Calcd for C11H15OBr: C, 54.34; H,
6.22. Found: C, 54.28; H, 6.24.
4.4.15. Cyclopentyl-(p-tolyl)methanol (3o). Colorless
1
liquid; H NMR d 7.17 (dd, 4H, Jˆ8.1 Hz), 4.34 (d, 1H,
Jˆ8.5 Hz), 2.33 (s, 3H), 2.25±1.12 (m, 10H); 13C NMR d
141.5, 137.1, 128.9, 126.4, 78.9, 47.5, 29.4, 25.5, 25.4, 21.1
HRMS: Calcd for C13H18O[M]1, 190.136. Found: m/z
190.137. Anal. Calcd for C13H18O: C, 82.06; H, 9.53.
Found: C, 81.92; H, 9.65.
4.4.23. 2-Methyl-1-( p-tolyl)butan-1-ol (3w). Colorless
oil.54 1H NMR: d 7.20 (d, 2H, Jˆ9.2 Hz), 7.11 (d, 2H,
Jˆ8.2 Hz), 4.42 (d, 0.40 H, Jˆ6.1 Hz), 2.32 (s, 3H), 2.03
(s, 1H), 1.74±0.83 (m, 6H), 0.71 (d, 3H, Jˆ6.7 Hz). 13C
NMR: d 140.9, 140.6, 136.9, 136.7, 128.7, 126.6, 126.3,
78.5, 78.0, 41.8, 41.5, 25.7, 24.9, 21.0, 15.9, 14.1, 11.6,
11.2.
4.4.16. 2-Norbornyl-phenylmethanol (3p). Colorless oil;51
1H NMR d 7.35±7.21 (m, 5H), 4.16 (d, 0.5H, Jˆ9.6 Hz),
4.10 (d, 0.5H, Jˆ10.0 Hz), 1.50±0.80 (m, 12H); 13C NMR d
144.5, 143.1, 128.2, 127.5, 127.4, 127.2, 126.8, 78.8, 49.9,
49.4, 38.7, 38.3, 35.8, 34.9, 34.2, 30.1, 29.9, 28.7.
4.4.24. 2-Methyl-1-(o-tolyl)butan-1-ol (3x). Colorless
oil.52 1H NMR: d 7.44±7.10 (m, 4H), 4.79 (d, 0.55 h,
Jˆ5.5 Hz), 4.67 (d, 0.45 H, Jˆ7.2 Hz), 2.33 (s, 1.5H),
2.31 (s, 1.5 H), 1.80±0.87 (m, 7H), 0.77 (d, 3H,
Jˆ6.8 Hz). 13C NMR: d 142.2, 135.1, 134.6, 130.2, 127.0,
126.9, 126.2, 126.1, 125.9, 74.8, 73.7, 41.1, 40.6, 26.4, 24.4,
19.4, 19.2, 15.4, 13.6, 11.9, 11.2.
4.4.17. 2-Norbornyl-(4-bromophenyl)methanol (3q).
Colorless oil; H NMR d 7.47±7.42 (m, 2H), 7.20±7.16
1
(m, 2H), 4.18 (d, 0.6H, Jˆ9.4 Hz), 4.10 (d, 0.4H,
Jˆ99 Hz), 2.48±0.84 (m, 12H); 13C NMR d 143.44, 142.l,

G. W. Kabalka et al. / Tetrahedron 57 (2001) 1663±1670
1669
4.4.25. 1-Phenylheptan-1-ol (3y). Colorless oil.55 1H NMR:
d 7.34±7.21 (m, 5H), 4.57 (t, 1H, Jˆ5.7 Hz), 2.40 (s, 1H),
1.77±0.84 (m, 13H). 13C NMR: d 144.9, 128.3, 127.3,
125.9, 74.5, 39.0, 31.7, 29.1, 25.7, 22.5, 14.0.
3. Larock, R. C. Comprehensive Organic Transformations,
VCH: New York, 1989 (pp 553±567).
4. Sweeny, J. B. In Comprehensive Organic Functional Group
Transformations, Katrizky, A. R., Meth-Cohn, O., Rees,
C. W., Ley, S. V., Eds.; Pergamon: Cambridge, 1995; Vol.
2, pp 37.
4.4.26. 1-(4-Fluorophenyl)heptan-1-ol (3z). Colorless oil.
1H NMR: d 7.30±6.96 (m, 4H), 4.58 (t, 1H, Jˆ6.4 Hz), 2.38
(s, 1H), 1.72±0.84 (m, 13H). 13C NMR: d 164.00, 160.1,
140.6, 140.6, 127.5, 127.4, 115.2, 114.9, 73.9, 39.1, 31.7,
29.1, 25.7, 22.5, 14.0. Anal. Calcd for C13H19OF: C, 74.25;
H, 9.11. Found: C, 74.31; H. 9.21.
5. Wake®eld, B. J. Organolithium Method, Academic: New
York, 1988.
6. Knochel, P.; Singer, R. D. Chem. Rev. 1993, 93, 2117.
7. Furukawa, J.; Kawabata, N. Adv. Organomet. Chem. 1974, 12,
103.
8. Reetz, M. T. Top. Curr. Chem. 1982, 106, 1.
9. Kauffmann, T.; Hamsen, A.; Beirich, C. Angew. Chem., Int.
Ed. Engl. 1982, 21, 144.
4.4.27. 1-(4-Chlorophenyl)heptan-1-ol (3aa). Colorless
oil.56 1H NMR: d 7.31 (d, 2H, Jˆ8.0 Hz), 7.24 (d, 2H,
Jˆ8.4 Hz), 4.60 (t, 1H, Jˆ6.4 Hz), 2.20 (s, 1H), 1.72±
0.84 (m, 13H). 13C NMR: d 143.4, 133.0, 128.5, 127.2,
73.9, 39.1, 31.7, 29.1, 25.6, 22.5, 14.0.
10. Reetz, M. T.; Steinbach, R.; Westermann, J.; Urz, R.;
Wenderoth, B.; Peter, R. Angew. Chem. Int. 1982, 21, 135.
11. Kauffmann, T.; Abel, T.; Schreer, M.; Wingbermuhle, D.
Tetrahedron 1987, 43, 2021.
4.4.28. 1-(2-Chlorophenyl)heptan-1-ol (3ab). Colorless
oil. 1H NMR: d 7.53±7.13 (m, 4H), 5.08 (t, 1H,
Jˆ4.9 Hz), 2.41 (s, 1H), 1.73±0.84 (m, 13H). 13C NMR:
d 142.4, 131.8, 129.3, 128.2, 127.0, 70.6, 37.6, 31.8, 29.1,
25.7, 22.6, 14.1. Anal. Calcd for C13H19OCl: C, 68.86; H,
8.44. Found: C, 68.61; H, 8.45.
12. Ikeda, Y.; Ukai, J.; Ikeda, N.; Yamamoto, H. Tetrahedron
1987, 43, 723.
13. Kauffmann, T.; Hopp, G.; Laarmann, B. Tetrahedron Lett.
1990, 31, 511.
14. Fukuzawa, S.; Tsuchimoto, T.; Tanai, T. Chem. Lett. 1994,
1981.
15. Kataoka, Y.; Makihira, I.; Utsunomiya, M.; Tani, K. J. Org.
Chem. 1997, 62, 8540.
4.4.29. 1-(4-Bromophenyl)heptan-1-ol (3ac). Colorless
oil.57 1H NMR: d 7.43 (d, 2H, Jˆ8.4 Hz), 7.16 (d, 2H,
Jˆ8.4 Hz), 4.56 (t, 1H, Jˆ6.5 Hz), 2.35 (s, 1H), 1.70±
0.84 (m, 13H). 13C NMR: d 143.8, 131.4, 127.6, 121.0,
73.9, 39.0, 31.7, 29.1, 25.6, 22.5, 14.0.
16. Roush, W. R.; Grover, P. T. J. Org. Chem. 1995, 60, 3806.
17. Brown, H. C.; Randad, R. A.; Bhat, K. S.; Zaidlewicz, M.;
Racherla, U. S. J. Am. Chem. Soc. 1990, 112, 2389.
18. Jacob, P.; Brown, H. C. J. Org. Chem. 1977, 42, 579.
19. Batey, R. A.; Mackay, D. B.; Santhakumar, V. J. Am. Chem.
Soc. 1999, 121, 5075.
4.4.30. 1-(p-Tolyl)heptan-1-ol (3ad). Colorless oil.58 1H
NMR: d 7.22 (d, 2H, Jˆ8.0 Hz), 7.14 (d, 2H, Jˆ8.0 Hz),
4.60 (t, 1H, Jˆ6.5 Hz), 2.34 (s, 3H), 1.88 (s, 1H), 1.82±0.84
(m, 13H). 13C NMR: d 142.0, 137.1, 129.0, 125.8, 74.5,
39.0, 31.7, 29.2, 25.8, 22.6, 21.1, 14.0.
20. Mikhailov, B. M.; Baryshnikova, T. K.; Shashkov, A. S.
J. Organomet. Chem. 1981, 219, 301.
21. Kabalka, G. W. Intra-Sci. Chem. Rep. 1973, 7, 57.
22. Miyaura, N.; Itoh, M.; Suzuki, A.; Brown, H. C.; Midland,
M. M.; Jacob, I. I. I. P. J. Am. Chem. Soc. 1972, 94, 6549.
23. Kabalka, G. W.; Maddox, J. T.; Bogas, E.; Kelly, S. W. J. Org.
Chem. 1997, 62, 3688.
4.4.31. 1-(o-Tolyl)heptan-1-ol (3ae). Colorless oil.59 1H
NMR: d 7.47±7.10 (m, 4H), 4.91 (t, 1H, Jˆ5.6 Hz), 2.33
(s, 3H), 1.81 (s, 1H), 1.75±0.84 (m, 13H). 13C NMR: d
143.1, 134.4, 130.1, 127.0, 126.2, 125.1, 70.7, 38.1, 31.8,
29.2, 26.0, 22.6, 19.0, 14.0.
24. Okada, K.; Hosoda, Y.; Oda, M. Tetrahedron Lett. 1986, 27,
6213.
25. Brown, H. C.; Kramer, G. W.; Ley, A. B.; Midland, M. M.
Organic Syntheses via Boranes, Wiley-Interscience: New
York, 1975 (p 11).
4.5. Reaction of dicyclohexylboron chloride with
4-bromobenzaldehyde in the presence of bases
26. Eleveld, M. B.; Hogevven, H. Tetrahedron Lett. 1984, 25,
5187.
Cyclohexyl-(4-bromophenyl)methanol (3e) was prepared
by the procedure described earlier using triethylamine,
2,6-lutidine, quinuclidine, DBU, n-butyllithium and
t-butoxide lithium as bases, and the yield of the desired
product is summarized in Table 2.
27. Mukaiyama, T.; Soai, K.; Sato, T.; Shimizu, H.; Suzuki, K.
J. Am. Chem. Soc. 1979, 101, 1455.
28. Mazalerrat, J. P.; Cram, D. J. J. Am. Chem. Soc. 1981, 103,
4585.
29. Oguni, N.; Omi, T. Tetrahedron Lett. 1984, 25, 2823.
30. Joshi, N. N.; Srebnik, M.; Brown, H. C. Tetrahedron Lett.
1989, 30, 5551.
Acknowledgements
31. Bhatt, M. V.; Kulkarni, S. U. Synthesis 1983, 249.
32. Mukaiyama, T. Org. React. 1982, 28, 203.
33. Evans, D. A.; Nelson, J. V.; Taber, T. R. Topics in Stereo-
chemistry, Vol. 2; Wiley: New York, 1982 (p 1).
34. Kim, B. M.; Williams, S. F.; Masamune, S. In Comprehensive
Organic Synthesis, Trost, B. M., Fleming, I., Eds.; Pergamon:
Oxford, 1991; Vol. 2 (239pp).
We wish to thank the US Department of Energy and the
Robert H. Cole Foundation for support of this research.
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